The rapid clinical development of antiretrovirals and antimicrobials for opportunistic infections will require a drug analysis facility with the capability to employ a variety of assay techniques. In addition, the movement toward an accelerated Phase I-II testing period will demand more efficient use of serum concentration data obtained from these studies. Therefore, this application seeks to establish an integrated approach to antiretroviral pharmacology with the following specific aims; 1. To provide a core pharmacology laboratory that will provide all necessary input for the design, conduct, drug analysis, pharmacokinetic analysis, and data interpretation of all AIDS Clinical Trials Group (ACTG) protocols with a pharmacology component within the Rochester AIDS Clinical Trials Unit (ACTU) and other selected sites when appropriate. 2. To establish a central laboratory with a validated assay for the most common antiretrovirals currently prescribed in ACTG protocols (zidovudine {ZDV}, dideoxyinosine {DDI}, and di,dehydro,dideoxythymidine {D4T}. 3. To provide a resource to the ACTG that is capable of developing and validating assay methodologies for new antiretrovirals, drugs for opportunistic infections or malignancies associated with HIV disease. 4. To integrate a broad-based antiretroviral laboratory analysis capability with the development of a population pharmacokinetics data base that will enable the detection of subpopulation differences in antiretroviral disposition. 5. To establish an antiretroviral serum concentration data base that can be utilized to investigate the relationship between drug exposure and clinical outcomes (ie, toxicity, survival, immunologic parameters, HIV resistance patterns) and evaluate the potential role of therapeutic drug monitoring for anti-HIV therapy.